Deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. Identification of the aggregated proteins provides insights into molecular pathogenesis. Beta-amyloid (Aβ) and tau aggregates are typically found in Alzheimer disease (AD). Alpha-synuclein in Lewy bodies is typically found in Parkinson disease (PD). Ubiquitin-positive, tau- and α-synuclein-negative inclusions are typical of frontotemporal lobar degeneration with ubiquitin-positive inclusions generally referred to as ubiquitin-positive frontotemporal lobar degeneration (FTLD-U). Ubiquitinated TDP-43 is found in frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). In AD, the amyloid cascade hypothesis and tau hypothesis dominate pathogenesis research. However, there is a need to further understand underlying etiology of the disease.
Mature messenger RNAs are derived from primary transcripts (pre-mRNAs) and undergo post-transcriptional processing such as 5′ end capping, removal of introns by splicing, and polyadenylation. Spliceosomes are RNA and protein complexes that catalyze splicing reactions. U1 small nuclear ribonucleoprotein (snRNP) is found in spliceosomes and expressed in humans. Functional U1 snRNP knockdown results in accumulated unspliced pre-mRNAs by genomic tiling microarrays. See Kaida et al., Nature, 2010, 468, 664-668.